The glycolipids dimeric Le.sup.x (difucosyl Y.sub.2 ; III.sup.3 FucV.sup.3 FucnLc.sub.6 Cer) and trimeric Le.sup.x (III.sup.3 FucV.sup.3 FucVII.sup.3 FucnLc.sub.8 Cer) are major antigens that are found in various human adenocarcinomas but are absent in corresponding normal tissue (Hakomori et al., 1984, J. Biol. Chem., 259, 4672-2680). A monoclonal antibody directed to those structures, but not cross-reacting with simple Le.sup.x (see Table I), is an important reagent for detecting the presence of the antigens in tumor cells (Fukushi et al., 1984, J. Biol. Chem., 259, 4681-4685; Fukushi et al. , 1984, J. Exp. Med., 159, 506-520) and in sera of patients with cancer. The antibody, however, reacts on immunohistochemistry or immunofluorescence with selected normal cells, such as epithelial cells of proximal convoluted tubules of kidney and weakly with some subpopulations of granulocytes (Fukushi et al., 1984, Cancer Res., 45, 3711-1717).
More recently, the antibody was found to react with granulocytes of inflammatory bone marrow adjacent to joints affected with rheumatoid arthritis (RA) (Ochi et al, 1988, J. Rheumatol., 15, 1609-1615). Intradermal inoculation of liposomes containing the glycoplipids suppresses the appearance of inflammatory granulocytes in the bone marrow of RA-affected joints with a subsequent reduction of RA symptoms.
Because of the presence of the antigens in high concentration in various types of human cancer and inflammatory processes, the antigens are expected to be useful components for developing anti-cancer and anti-inflammatory vaccines. To support this idea, reconstituted Newcastle's Disease virus membrane including the dimeric Le.sup.x antigen induced an immune response that suppressed growth of murine tumors bearing Le.sup.x.
Le.sup.y antigens, including extended Le.sup.y (Le.sup.y octasaccharide ceramide) and trifucosyl Le.sup.y, are also important human cancer antigens and are expected to be useful components for developing anti-cancer vaccines.
Thus the demand for Le.sup.x dimeric Le.sup.x and sialylated forms thereof and for various types of Le.sup.y antigen for use in active immunization has been increasing. However, it has been available only from human cancer tissue or via chemical synthesis as described by Nilsson & Norberg (1987, Glycoconjugate J., 4, 219-223; and 1988, Carbohydr. Res., 183, 71-82), Sato et al. (1987, Carbohydr. Res., 167, 197-210; 1988, Tetrahedron Lett., 29, 5267-5270) and Nicolaou et al. (1990, J. Am. Chem. Soc., 112, 3693-3695).
Preparations from tumor cells provide limited quantities which often contain impurities. On the other hand, pure chemical synthesis involves at least 50 steps, is extremely laborious and results in a poor final yield.
It is toward the objective of providing a low-cost, simplified and greater-yielding synthesis of Le.sup.x ; dimeric and trimeric Le.sup.x antigens; sialylated forms thereof; and Le.sup.y antigen that the present invention is directed.